The objectives of our research are to characterize canine lymphocyte subpopulations and monocytes and to define their roles in mediating and abrogating transfusion-related sensitization and resistance to allogeneic marrow grafts. Specifically, lymphocyte subsets and monocytes will be defined using phenotypic and functional markers. Phenotypic markers will include flourescence staining for surface immunoglobulin and antigens recognized by monoclonal antibodies and rosette formation with human red blood cells. Secondly, cells thus defined will be separated by cytolytic treatment, adherence to antibody-coated or -uncoated plates, density gradients and the fluorescence-activated cell sorter, and studied in vitro in functional assays such as mixed leukocyte cultures, cell-mediated lympholysis, plaque formation in gel and regulation of hemopoiesis. Thirdly, in vivo marrow grafting experiments will test which of the cells so defined will induce sensitization resulting in subsequent marrow graft rejection and which cells are involved in mediating resistance or, vice versa, which cells are able to abrogate resistance to histoincompatible marrow grafts in nonsensitized dogs. The long-term goal is to apply the knowledge gained from these studies to marrow transplantation in man where it has been shown that sustained engraftment may be difficult to achieve in patients with aplastic anemia transfused before grafting and giving histocompatible grafts and in patients with aplastic anemia or leukemia, not transfused before grafting, who are given histoincompatible grafts. Engraftment is even more difficult to achieve when, in an attempt to prevent graftversus-host disease, T lymphocyte-depleted marrow is transplanted.